AI Article Synopsis
- Stem cells possess essential traits like proliferation and differentiation, which are maintained by genetic and epigenetic factors, with super-enhancers (SEs) playing a key role in preserving these traits through a specialized transcriptional model.
- The study introduces "super-enhancer omics," exploring the organization and function of SEs and their relationship with stem cell characteristics such as identity, self-renewal, and oncogenic alterations linked to cancer stem cells.
- Potential therapeutic strategies targeting components of the SE complex (like small molecules or genome editing) are discussed for treating diseases, particularly cancer, and the review emphasizes future directions in stem cell research through the lens of SEs.
Article Abstract
The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of "super-enhancer omics", inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293198 | PMC |
| http://dx.doi.org/10.1186/s12943-024-02066-z | DOI Listing |
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